Bladder CancerPhase 2MARINE-01NCT07307456
Toripalimab Combined With BCG Perfusion for the Treatment of HR-NMIBC After TURBT Surgery Exploration
A Phase 2 study testing Treatment with toripalimab combined with BCG perfusion following transurethral resection of bladder tumor (TURBT) in people with Bladder Cancer, run by Changhai Hospital at 1 site in China.
Trial summary
This is a single-center, prospective, open-label, non-randomized clinical study initiated and conducted by the Department of Urology, Shanghai Changhai Hospital. The Principal Investigators are Professor Zhang Zhensheng and Professor Chen Guanghua. The projected study period is from December 2025 to December 2028. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Bladder Cancer
- What is being tested?
- Treatment with toripalimab combined with BCG perfusion following transurethral resection of bladder tumor (TURBT)
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 31 participants
- Where
- 1 siteChina
- Study dates
- 8 Dec 2025to 8 Dec 2028
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age 18-75 years.
- Patients with a pathological diagnosis of high-risk or very high-risk non-muscle-invasive bladder cancer (NMIBC) following transurethral resection or cystoscopic biopsy.
- "High-risk patients" must meet any one of the following criteria:
- All T1 high-grade (HG)/G3 without carcinoma in situ (CIS), excluding those in the very high-risk group.
- All CIS patients, excluding those in the very high-risk group.
- Ta low-grade (LG)/G2 or T1 G1 without CIS, accompanied by three risk factors.
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- Ta HG/G3 or T1 LG without CIS, accompanied by at least two risk factors.
- T1 G2 without CIS, accompanied by at least one risk factor. "Very high-risk patients" must meet any one of the following criteria:
- Ta HG/G3 with CIS accompanied by three risk factors. (2) T1 G2 with CIS accompanied by at least two risk factors. (3) T1 HG/G3 with CIS accompanied by at least one risk factor. (4) T1 HG/G3 without CIS, accompanied by three risk factors. (Risk factors: age >70 years; tumor diameter >3 cm; multiple papillary carcinomas) 3. No prior treatment with therapies targeting PD-1, PD-L1, PD-L2, or CTLA-4, or other antibodies or drugs specifically targeting T-cell co-stimulation or checkpoint pathways (immune checkpoint blockers), or bacille Calmette-Guérin (BCG) therapy.
- 4. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. 5. Adequate organ function, defined as meeting the following criteria (within 14 days prior to enrollment, without transfusion or granulocyte colony-stimulating factor treatment): "Hematology": i. Absolute neutrophil count (ANC) ≥1,000/mm³ ii. Platelet count ≥75,000/mm³ iii. Hemoglobin ≥8.0 g/dL "Hepatic function": i. Total bilirubin ≤1.5 × upper limit of normal (ULN) OR direct bilirubin ≤ ULN for subjects with total bilirubin >1.5 × ULN.
- Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤2.5 × ULN.
- "Renal function": Creatinine clearance (CrCl) >30 mL/min, calculated using the Cockcroft-Gault formula.
- 6. Female subjects of childbearing potential must have a negative urine or serum pregnancy test within 7 days prior to enrollment, be willing to use effective contraception during the study period and for at least 6 months after the last dose of study drug (including chemotherapy agents and toripalimab). Male subjects with female partners of childbearing potential must agree to use effective contraception during the study period and for at least 6 months after the last dose.
- 7. Subjects voluntarily agree to participate in the study by providing written informed consent, demonstrate good compliance, and are willing to cooperate with follow-up.
Who cannot join
- Patients meeting any of the following criteria were excluded from this study:
- History or presence of muscle-invasive or disseminated/metastatic bladder cancer. Patients with locally advanced or metastatic bladder cancer or concurrent upper tract urothelial carcinoma were excluded.
- Prior surgical intervention for bladder cancer other than transurethral resection of bladder tumor (TURBT) and/or bladder biopsy.
- Administration of any other approved systemic anticancer therapy or systemic immunomodulatory agents (including, but not limited to, interferon, interleukin-2, and tumor necrosis factor) within 28 days prior to enrollment.
- Severe chronic or active infection requiring systemic antibacterial, antifungal, or antiviral therapy within 14 days prior to enrollment.
- Major surgery or significant trauma within 28 days prior to enrollment.
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- Vaccination with a live vaccine within 28 days prior to enrollment.
- Use of any Chinese herbal medicine or proprietary Chinese medicine for cancer control within 14 days prior to enrollment.
- Treatment with systemic corticosteroids within 4 weeks prior to the study intervention.
- Active autoimmune diseases requiring systemic treatment or other conditions necessitating long-term use of high-dose corticosteroids and other immunosuppressive agents.
- History of potassium, sodium, or calcium abnormalities, hypoalbuminemia, interstitial lung disease, non-infectious pneumonitis, or other uncontrolled systemic diseases (including diabetes, hypertension, cardiovascular diseases, etc.) that, in the investigator's judgment, could affect the treatment.
- Active viral hepatitis B or C. Patients with acute or chronic active hepatitis B or C infection were excluded if they met any of the following criteria: hepatitis B virus (HBV) DNA >2000 IU/mL or 10⁴ copies/mL; hepatitis C virus (HCV) RNA >10³ copies/mL; or co-positivity for hepatitis B surface antigen (HBsAg) and anti-HCV antibody.
- Known history of human immunodeficiency virus (HIV) infection or known diagnosis of acquired immunodeficiency syndrome (AIDS) (no screening tests were required).
- History of any organ transplantation, including allogeneic stem cell transplantation, except for transplants not requiring immunosuppression (e.g., corneal transplant, hair transplant).
- Known history of allergic reactions to any of the study drugs.
- Concurrent participation in another clinical trial.
- History and/or concurrent presence of other malignancies, except for: malignancies treated with curative intent with no recurrence for over 3 years, or early-stage cancers considered cured, including completely resected basal cell and squamous cell skin cancers, and completely resected carcinoma in situ of any type.
- Active central nervous system metastases or carcinomatous meningitis.
- Any condition that, in the investigator's opinion, rendered the patient unsuitable for study participation (e.g., treatment not in the patient's best interest, poor patient compliance, etc.).
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
China1 site, 1 recruiting
- Recruiting
ChangHai Hospital
Shanghai, Shanghai Municipality, 200433
About this study
Official title: A Prospective, Open-label, Single-center Clinical Study Evaluating the Efficacy and Safety of Toripalimab Combined With BCG Perfusion as an Adjuvant Treatment After TURBT in High-risk/Very High-risk Non-muscle-invasive Bladder Cancer
This is a single-center, prospective, open-label, non-randomized clinical study initiated and conducted by the Department of Urology, Shanghai Changhai Hospital. The Principal Investigators are Professor Zhang Zhensheng and Professor Chen Guanghua. The projected study period is from December 2025 to December 2028. This study aims to evaluate the efficacy and safety of toripalimab (a PD-1 inhibitor) combined with Bacillus Calmette-Guérin (BCG) intravesical instillation as adjuvant therapy following transurethral resection of bladder tumor (TURBT) in patients with high-risk/very high-risk non-muscle-invasive bladder cancer (NMIBC).
Bladder cancer is a common malignancy of the urinary system, with NMIBC accounting for approximately 75% of initial diagnoses. For high-risk patients who are unresponsive to or experience recurrence after BCG therapy, radical cystectomy remains the standard treatment. However, this procedure is associated with high rates of complications, mortality risk, and significantly negative impacts on quality of life. Therefore, exploring novel combination strategies that effectively reduce recurrence while preserving the bladder is of great clinical importance. This study is based on the successful application of immune checkpoint inhibitors in advanced urothelial carcinoma and recent Phase III trials (e.g., the CREST study) demonstrating the efficacy and safety of combining PD-1/PD-L1 inhibitors with BCG in treatment-naïve high-risk NMIBC. It seeks to investigate the potential of the domestic PD-1 inhibitor toripalimab in combination with standard BCG instillation.
Read more
The study plans to enroll 31 patients with histologically confirmed high-risk/very high-risk NMIBC who have not previously received immune checkpoint inhibitors or BCG therapy. All enrolled patients will first receive a single instillation of gemcitabine (2000mg), followed by the combination therapy phase: toripalimab (240mg, intravenous infusion, every 3 weeks for 8 cycles) combined with BCG intravesical instillation (induction phase for 6 weeks, maintenance phases at months 3 and 6). The primary efficacy endpoint is the pathological complete response (CR) rate at approximately 6 months after treatment initiation. Secondary efficacy endpoints include duration of CR, 6-month and 2-year event-free survival (EFS) rates, 1-year and 2-year cancer-specific survival (CSS) rates, time to radical cystectomy, and overall survival (OS). Safety endpoints encompass the incidence and severity of adverse events (AEs) and serious adverse events (SAEs).
Statistical analyses will be based on the Full Analysis Set (FAS) and Per-Protocol Set (PPS). The sample size calculation for the primary endpoint (6-month CR rate) is based on historical data assumptions, employing a one-sided test. Safety analyses will include all patients who received at least one dose of study treatment. This study will strictly adhere to the principles of the Declaration of Helsinki, Chinese Good Clinical Practice (GCP) guidelines, and relevant regulations. The study protocol has been submitted for review and approval by the Institutional Review Board (IRB)/Ethics Committee. Written informed consent will be obtained from all patients prior to participation. This study aims to provide a new and potentially more effective bladder-preserving treatment option for patients with high-risk/very high-risk NMIBC and to evaluate the safety profile of this combination regimen.
- Conditions
- Bladder Cancer
- Being tested
- Treatment with toripalimab combined with BCG perfusion following transurethral resection of bladder tumor (TURBT)
- Keywords
- HR-NMIBC, Immunotherapy, BCG, Bladder preservation treatment
- Medical subject headings
- Urinary Bladder Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Treatment with toripalimab combined with BCG perfusion following transurethral resection of bladder tumor (TURBT)Drug
This study employs a fixed-dose combination regimen. All enrolled patients with high-risk/very high-risk NMIBC, following TURBT, first receive a single 2000mg gemcitabine intravesical instillation. Subsequently, they undergo synchronized combination therapy consisting of fixed-dose 240mg toripalimab via intravenous infusion (every 3 weeks for 8 cycles) paired with standard BCG intravesical instillation (6-week induction phase + maintenance phases at months 3 and 6). Treatment continues until completion of the planned cycles, disease progression, or unacceptable toxicity. The protocol includes detailed dose-modification guidelines for immune-related adverse events based on CTCAE v5.0.
| Study group | Role | What they receive |
|---|---|---|
| Treatment with toripalimab combined with BCG instillation after TURBT in patients with HR - NMIBC | Other | Not described Receives: Drug: Treatment with toripalimab combined with BCG perfusion following transurethral resection of bladder tumor (TURBT) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Six - month pathological complete remission (CR) rate
(assessed via cystoscopy and urine cytology approximately six months after the first administration of the study drug)
Measured: From the first administration of the investigational drug to six months after the treatment.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Dec 2025
- Study start8 Dec 2025
- Primary completion8 Dec 2027 (estimated)
- Study completion8 Dec 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Bladder CancerStudies of the same condition, open and under way.
- More trials run by Changhai HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 31 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Changhai Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Shuxiong Zeng, Changhai Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07307456
- Sponsor's protocol ID
- KTSB20250508008
- Acronym
- MARINE-01
- Status last verified
- Dec 2025
- First submitted
- 14 Dec 2025
- Last updated
- 21 Jul 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 21 Jul 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Prospective, Open-label, Single-center Clinical Study Evaluating the Efficacy and Safety of Toripalimab Combined With BCG Perfusion as an Adjuvant Treatment After TURBT in High-risk/Very High-risk Non-muscle-invasive Bladder Cancer
- ClinicalTrials.gov ID
- NCT07307456
- Acronym / sponsor ID
- MARINE-01 / KTSB20250508008
- Conditions
- Bladder Cancer
- Keywords
- HR-NMIBC, Immunotherapy, BCG, Bladder preservation treatment
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 31 participants (estimated)
- Lead sponsor
- Changhai HospitalUniversity, hospital or other
- Study start
- 8 Dec 2025 (actual)
- Primary completion
- 8 Dec 2027 (estimated)
- Study completion
- 8 Dec 2028 (estimated)
- First posted
- 29 Dec 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is a single-center, prospective, open-label, non-randomized clinical study initiated and conducted by the Department of Urology, Shanghai Changhai Hospital. The Principal Investigators are Professor Zhang Zhensheng and Professor Chen Guanghua. The projected study period is from December 2025 to December 2028. This study aims to evaluate the efficacy and safety of toripalimab (a PD-1 inhibitor) combined with Bacillus Calmette-Guérin (BCG) intravesical instillation as adjuvant therapy following transurethral resection of bladder tumor (TURBT) in patients with high-risk/very high-risk non-muscle-invasive bladder cancer (NMIBC).
Bladder cancer is a common malignancy of the urinary system, with NMIBC accounting for approximately 75% of initial diagnoses. For high-risk patients who are unresponsive to or experience recurrence after BCG therapy, radical cystectomy remains the standard treatment. However, this procedure is associated with high rates of complications, mortality risk, and significantly negative impacts on quality of life. Therefore, exploring novel combination strategies that effectively reduce recurrence while preserving the bladder is of great clinical importance. This study is based on the successful application of immune checkpoint inhibitors in advanced urothelial carcinoma and recent Phase III trials (e.g., the CREST study) demonstrating the efficacy and safety of combining PD-1/PD-L1 inhibitors with BCG in treatment-naïve high-risk NMIBC. It seeks to investigate the potential of the domestic PD-1 inhibitor toripalimab in combination with standard BCG instillation.
The study plans to enroll 31 patients with histologically confirmed high-risk/very high-risk NMIBC who have not previously received immune checkpoint inhibitors or BCG therapy. All enrolled patients will first receive a single instillation of gemcitabine (2000mg), followed by the combination therapy phase: toripalimab (240mg, intravenous infusion, every 3 weeks for 8 cycles) combined with BCG intravesical instillation (induction phase for 6 weeks, maintenance phases at months 3 and 6). The primary efficacy endpoint is the pathological complete response (CR) rate at approximately 6 months after treatment initiation. Secondary efficacy endpoints include duration of CR, 6-month and 2-year event-free survival (EFS) rates, 1-year and 2-year cancer-specific survival (CSS) rates, time to radical cystectomy, and overall survival (OS). Safety endpoints encompass the incidence and severity of adverse events (AEs) and serious adverse events (SAEs).
Statistical analyses will be based on the Full Analysis Set (FAS) and Per-Protocol Set (PPS). The sample size calculation for the primary endpoint (6-month CR rate) is based on historical data assumptions, employing a one-sided test. Safety analyses will include all patients who received at least one dose of study treatment. This study will strictly adhere to the principles of the Declaration of Helsinki, Chinese Good Clinical Practice (GCP) guidelines, and relevant regulations. The study protocol has been submitted for review and approval by the Institutional Review Board (IRB)/Ethics Committee. Written informed consent will be obtained from all patients prior to participation. This study aims to provide a new and potentially more effective bladder-preserving treatment option for patients with high-risk/very high-risk NMIBC and to evaluate the safety profile of this combination regimen.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Treatment with toripalimab combined with BCG instillation after TURBT in patients with HR - NMIBC | Other | Drug: Treatment with toripalimab combined with BCG perfusion following transurethral resection of bladder tumor (TURBT) |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (14 listed)
- Age 18-75 years.
- Patients with a pathological diagnosis of high-risk or very high-risk non-muscle-invasive bladder cancer (NMIBC) following transurethral resection or cystoscopic biopsy.
- All T1 high-grade (HG)/G3 without carcinoma in situ (CIS), excluding those in the very high-risk group.
- All CIS patients, excluding those in the very high-risk group.
- Ta low-grade (LG)/G2 or T1 G1 without CIS, accompanied by three risk factors.
Key exclusion criteria (19 listed)
- History or presence of muscle-invasive or disseminated/metastatic bladder cancer. Patients with locally advanced or metastatic bladder cancer or concurrent upper tract urothelial carcinoma were excluded.
- Prior surgical intervention for bladder cancer other than transurethral resection of bladder tumor (TURBT) and/or bladder biopsy.
- Administration of any other approved systemic anticancer therapy or systemic immunomodulatory agents (including, but not limited to, interferon, interleukin-2, and tumor necrosis factor) within 28 days prior to enrollment.
- Severe chronic or active infection requiring systemic antibacterial, antifungal, or antiviral therapy within 14 days prior to enrollment.
- Major surgery or significant trauma within 28 days prior to enrollment.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Treatment with toripalimab combined with BCG perfusion following transurethral resection of bladder tumor (TURBT)This study employs a fixed-dose combination regimen. All enrolled patients with high-risk/very high-risk NMIBC, following TURBT, first receive a single 2000mg gemcitabine intravesical instillation. Subsequently, they undergo synchronized combination therapy consisting of fixed-dose 240mg toripalimab via intravenous infusion (every 3 weeks for 8 cycles) paired with standard BCG intravesical instillation (6-week induction phase + maintenance phases at months 3 and 6). Treatment continues until completion of the planned cycles, disease progression, or unacceptable toxicity. The protocol includes detailed dose-modification guidelines for immune-related adverse events based on CTCAE v5.0. | Drug | Treatment with toripalimab combined with BCG instillation after TURBT in patients with HR - NMIBC |
Primary outcome
Six - month pathological complete remission (CR) rate
Time frame: From the first administration of the investigational drug to six months after the treatment.
(assessed via cystoscopy and urine cytology approximately six months after the first administration of the study drug)
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Jul 2026.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Treatment with toripalimab combined with BCG perfusion following transurethral resection of bladder tumor (TURBT) in people with Bladder Cancer, run by Changhai Hospital at 1 site in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 14 inclusion and 19 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 21 Jul 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Shuxiong Zeng, Doctor (86-18930568759, zengshuxiong@126.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Six - month pathological complete remission (CR) rate (time frame: From the first administration of the investigational drug to six months after the treatment.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 Jul 2026.